ArticleFEBS open bio2019
Regorafenib reverses HGF-induced sorafenib resistance by inhibiting epithelial-mesenchymal transition in hepatocellular carcinoma.
Article in FEBS open bio, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Unraveling regorafenib resistance: metabolic reprogramming, tumor plasticity, and novel approaches to overcome therapy failure.Archives of pharmacal research · 2026Review
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- CUL1-neddylation contributes to K29-linked ubiquitination on p27 for autophagic degradation in sorafenib-resistant liver cancer.Cell biology and toxicology · 2025Article
- Lenvatinib-resistant hepatocellular carcinoma promotes malignant potential of tumor-associated macrophages via exosomal miR-301a-3p.Annals of gastroenterological surgery · 2024Article
- Sorafenib plus memory-like natural killer cell immunochemotherapy boosts treatment response in liver cancer.BMC cancer · 2024Article
- Review
- IL-22 signaling promotes sorafenib resistance in hepatocellular carcinoma via STAT3/CD155 signaling axis.Frontiers in immunology · 2024Article
- EMT-related gene risk model establishment for prognosis and drug treatment efficiency prediction in hepatocellular carcinoma.Scientific reports · 2023Article
- [Research progress on the mechanism and response strategies of molecular targeted drug resistance in liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Camptothecin improves sorafenib sensitivity by inhibiting Nrf2‑ARE pathway in hepatocellular carcinoma.Oncology reports · 2023Article
- The Roles of Epigenetic Regulation and the Tumor Microenvironment in the Mechanism of Resistance to Systemic Therapy in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- ETS-1/c-Met drives resistance to sorafenib in hepatocellular carcinoma.American journal of translational research · 2023Article
- Review
- Corrigendum to: Regorafenib reverses HGF-induced sorafenib resistance by inhibiting epithelial-mesenchymal transition in hepatocellular carcinoma.FEBS open bio · 2022Article
- Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells.Experimental and therapeutic medicine · 2022Article
- Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment.Cancer cell international · 2022Review
- Review
- XRCC2 reduced the sensitivity of NSCLC to radio-chemotherapy by arresting the cell cycle.American journal of translational research · 2022Article
- Autophagy-Related Chemoprotection against Sorafenib in Human Hepatocarcinoma: Role of FOXO3 Upregulation and Modulation by Regorafenib.International journal of molecular sciences · 2021Article
- Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection.Biomedicines · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib resistance is one of the major obstacles towards achieving a better outcome in patients with advanced hepatocellular carcinoma (HCC), in which aberrant activation of the hepatocyte growth factor (HGF)/mesenchymal-epithelial transition pathway is frequently observed. Here, we report that HCC cells develop sorafenib resistance following HGF stimulation. Furthermore, HGF activates the downstream extracellular signal-related kinase (ERK) and signal transducer and activator of transcription 3 (STAT3) pathway and induces epithelial-mesenchymal transition (EMT) by up-regulating Snail in HCC cells. Inhibition of ERK and STAT3 abolished the rescue effect of HGF by down-regulating Snail and EMT. Moreover, phosphoinositide 3-kinase/Akt was also activated in HGF-treated HCC cells, although it had no effect on Snail expression. Notably, we also found that regorafenib reversed HGF-induced sorafenib resistance by inhibiting ERK and STAT3, and subsequently down-regulating Snail and EMT. Taken together, our results indicate that HGF induces sorafenib resistance by activating phosporylated (P)-ERK/Snail/EMT and P-STAT3/Snail/EMT pathways. Inhibition of P-ERK and P-STAT3 by regorafenib can block HGF-induced EMT, thereby reversing HGF-induced sorafenib resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.